| First Author | Oliveras-Salvá M | Year | 2014 |
| Journal | Neurobiol Aging | Volume | 35 |
| Issue | 11 | Pages | 2625-2636 |
| PubMed ID | 25037286 | Mgi Jnum | J:218067 |
| Mgi Id | MGI:5616505 | Doi | 10.1016/j.neurobiolaging.2014.04.032 |
| Citation | Oliveras-Salva M, et al. (2014) Alpha-synuclein-induced neurodegeneration is exacerbated in PINK1 knockout mice. Neurobiol Aging 35(11):2625-2636 |
| abstractText | Loss-of-function mutations in the PINK1 gene lead to recessive forms of Parkinson's disease. Animal models with depleted PINK1 expression have failed to reproduce significant nigral dopaminergic neurodegeneration and clear alpha-synuclein pathology, main characteristics of the disease. In this study, we investigated whether alpha-synuclein pathology is altered in the absence of PINK1 in cell culture and in vivo. We observed that downregulation of PINK1 enhanced alpha-synuclein aggregation and apoptosis in a neuronal cell culture model for synucleinopathy. Silencing of PINK1 expression in mouse substantia nigra using recombinant adeno-associated viral vectors did not induce dopaminergic neurodegeneration in a long-term study up to 10 months, nor did it enhance or accelerate dopaminergic neurodegeneration after alpha-synuclein overexpression. However, in PINK1 knockout mice, overexpression of alpha-synuclein in the substantia nigra resulted in enhanced dopaminergic neurodegeneration as well as significantly higher levels of alpha-synuclein phosphorylation at serine 129 at 4 weeks postinjection. In conclusion, our results demonstrate that total loss of PINK1 leads to an increased sensitivity to alpha-synuclein-induced neuropathology and cell death in vivo. |
